3IQL

Crystal structure of the rat endophilin-A1 SH3 domain

3IQL の概要

• エントリーDOI: 10.2210/pdb3iql/pdb
• 関連するPDBエントリー: 2knb
• 分子名称: Endophilin-A1, CHLORIDE ION (3 entities in total)
• 機能のキーワード: sh3, endophilin, coiled coil, cytoplasm, endocytosis, lipid-binding, membrane, phosphoprotein, sh3 domain, protein binding
• 由来する生物種: Rattus norvegicus (brown rat,rat,rats)
• 細胞内の位置: Cytoplasm: O35179
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 16034.49

構造登録者

Trempe, J.F.,Kozlov, G.,Camacho, E.M.,Gehring, K. (登録日: 2009-08-20, 公開日: 2009-11-10, 最終更新日: 2023-09-06)

主引用文献

Trempe, J.F.,Chen, C.X.,Grenier, K.,Camacho, E.M.,Kozlov, G.,McPherson, P.S.,Gehring, K.,Fon, E.A.
SH3 domains from a subset of BAR proteins define a Ubl-binding domain and implicate parkin in synaptic ubiquitination.
Mol.Cell, 36:1034-1047, 2009

PubMed Abstract: Mutations in the parkin gene are responsible for a common inherited form of Parkinson's disease (PD). Parkin is a RING-type E3 ubiquitin ligase with an N-terminal ubiquitin-like domain (Ubl). We report here that the parkin Ubl binds SH3 domains from endocytic BAR proteins such as endophilin-A with an affinity comparable to proline-rich domains (PRDs) from well-established SH3 partners. The NMR structure of the Ubl-SH3 complex identifies the PaRK extension, a unique C-terminal motif in the parkin Ubl required for SH3 binding and for parkin-mediated ubiquitination of endophilin-A in vitro. In nerve terminals, conditions that promote phosphorylation enhance the interaction between parkin and endophilin-A and increase the levels of ubiquitinated proteins within PRD-associated synaptic protein complexes in wild-type but not parkin knockout brain. The findings identify a pathway for the recruitment of synaptic substrates to parkin with the potential to explain the defects in synaptic transmission observed in recessive forms of PD.

PubMed: 20064468
DOI: 10.1016/j.molcel.2009.11.021

実験手法

X-RAY DIFFRACTION (1.4 Å)